4-Demethoxydaunorubicin is an anthracycline derivative known to have antitumor activity as reported by F. Arcamone et al. in Cancer Treatment Reports, Vol. 60(7), pages 829-834 (1976). Several syntheses of 4-demethoxydaunomycinone from 4-demethoxy-7,9-dideoxydaunomycinone have been described in the literature. See, for example, Suzuki et al., Tetrahedron Letters, p. 2303 (1977) and Kerdesky et al., J. American Chem. Soc., 100(11), p. 3635 (1978).
In the past, little effort was expended in the preparation of optically active aglycones. Such optically active compounds would avoid the very complex separation of diastereomeric products in the final glycosidation step and, of course, would save the valuable sugar moiety.
Past procedures used to obtain optically active aglycones make use of an optically active tetralin as an A B synthon, that has been prepared by resolution of racemic material, as shown in Arcamone et al. German Pat. No. 2,601,785 or Broadhurst et al. J.C.S. Chem. Commun. p. 158 (1982), or by asymmetric systhesis, as shown by Terashima et al. Tetrahedron Letters, p. 2753 (1980) or Warrener et al. J.C.S. Chem. Commun. p. 1100 (1981). The chiral bicyclic compound is then transformed into a tetracyclic intermediate using the synthetic sequence shown in Wong et al., Canadian J. Chem. 49, p. 2712 (1971). This approach suffers from a lack of regiochemical control in the preparation of ring D substituted anthracyclinones, and results in very difficult to achieve regioisomer separation as shown by Wong et al. Canadian J. Chem. 51, p. 466 (1973).